Song Honglin, Koessler Thibaud, Ahmed Shahana, Ramus Susan J, Kjaer Susanne Krüger, Dicioccio Richard A, Wozniak Eva, Hogdall Estrid, Whittemore Alice S, McGuire Valerie, Ponder Bruce A J, Turnbull Clare, Hines Sarah, Rahman Nazneen, Eeles Rosalind A, Easton Douglas F, Gayther Simon A, Dunning Alison M, Pharoah Paul D P
CR-UK Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom.
Cancer Res. 2008 Nov 1;68(21):8837-42. doi: 10.1158/0008-5472.CAN-08-2363.
Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies.
最近通过全基因组关联研究确定了几个前列腺癌易感基因座。这些基因座是其他上皮性癌症易感性的候选基因座。本研究的目的是检测这些标签单核苷酸多态性(SNP)与侵袭性卵巢癌、结直肠癌和乳腺癌的关联性。在卵巢癌(2087例/3491例对照)、结直肠癌(2148例/2265例对照)和乳腺癌(第一组,4339例/4552例对照;第二组,3800例/3995例对照)病例对照研究中对12个前列腺癌相关标签SNP进行了基因分型。主要的关联性检验是病例组和对照组之间基因型频率的比较,并在适当情况下进行按研究分层的趋势检验。通过逻辑回归估计基因型特异性比值比(OR)。SNP rs2660753(染色体3p12)显示出与卵巢癌有关联的证据[每小等位基因OR,1.19;95%置信区间(95%CI),1.04 - 1.37;P(趋势)=0.012]。这种关联在浆液性组织学亚型中更强(OR,1.29;95%CI,1.09 - 1.53;P = 0.003)。SNP rs7931342(染色体11q13)显示出与乳腺癌有关联的一些证据(每小等位基因OR,0.95;95%CI,0.91 - 0.99;P(趋势)=0.028)。这种关联在雌激素受体阳性肿瘤中稍强(OR,0.92;95%CI,0.87 - 0.98;P = 0.011)。这些标签SNP均与结直肠癌风险无关。总之,与前列腺癌风险相关的基因座也可能与卵巢癌和乳腺癌易感性有关。然而,这些影响较小,需要在更大规模的研究中进行重复验证。